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Stilbene Synthesis by Mizoroki–Heck Coupling Reaction Under Microwave Irradiation

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Stilbene Synthesis by Mizoroki–Heck Coupling Reaction Under Microwave Irradiation An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation Carolina S. García, Paula M. Uberman and Sandra E. Martín* Full Research Paper Open Access Address: Beilstein J. Org. Chem. 2017, 13, 1717–1727. INFIQC-CONICET- Universidad Nacional de Córdoba, Departamento doi:10.3762/bjoc.13.166 de Química Orgánica, Facultad de Ciencias Químicas, Haya de la Torre y Medina Allende, Ciudad Universitaria, X5000HUA, Córdoba, Received: 25 April 2017 Argentina Accepted: 04 August 2017 Published: 18 August 2017 Email: Sandra E. Martín* - [email protected] Associate Editor: L. Vaccaro * Corresponding author © 2017 García et al.; licensee Beilstein-Institut. License and terms: see end of document. Keywords: aqueous reaction medium; MAOS; Mizoroki–Heck reaction; Pd nanoparticle; sustainable organic synthesis Abstract Aqueous Mizoroki–Heck coupling reactions under microwave irradiation (MW) were carried out with a colloidal Pd nanocatalyst stabilized with poly(N-vinylpyrrolidone) (PVP). Many stilbenes and novel heterostilbenes were achieved in good to excellent yields starting from aryl bromides and different olefins. The reaction was carried out in a short reaction time and with low catalyst loading, leading to high turnover frequency (TOFs of the order of 100 h−1). The advantages like operational simplicity, high robust- ness, efficiency and turnover frequency, the utilization of aqueous media and simple product work-up make this protocol a great option for stilbene syntheses by Mizoroki–Heck reaction. Introduction Palladium-catalyzed reactions have emerged as an important basic types of Pd-catalyzed reactions, particularly the vinyl- tool for organic synthesis. Among them, cross-coupling and ation of aryl/vinyl halides or triflates [7-10], explored not only coupling reactions have been broadly applied for C–C and in the inter- and intramolecular version [2,11-13], but also in C–heteroatom bond formation [1-6]. These reactions have been domino [14] and asymmetric catalytic processes [15]. Due to its proven to be powerful and attractive synthetic methods due to versatility, the Mizoroki–Heck reaction is extensively em- their high selectivity and tolerance to a wide range of func- ployed in the synthesis of pharmaceutical, agrochemical and tional groups on both coupling partners. The Mizoroki–Heck natural products, and continues to attract attention within the reaction and related chemistry occupy a special place among the synthetic chemists’ community [16-18]. 1717 Beilstein J. Org. Chem. 2017, 13, 1717–1727. From an economic and environmental standpoint, it is highly temperature via direct electroreduction of aqueous H2PdCl4 in desirable to develop more environmentally friendly synthetic the presence of poly(N-vinylpirrolidone) (PVP) [46,47]. These methodologies. Several studies were dedicated to the design of Pd NPs exhibited highly efficient catalytic activity in a novel catalytic system, that are more accessible, robust, effi- Suzuki–Miyaura coupling reactions [46,47] and nitroaromatic cient and ligand-free [19]. In that sense, nanoparticles (NPs) of hydrogenations [48] in aqueous medium. Outstanding perfor- transition metals have been introduced as eco-catalysts in mance of these PVP-Pd NPs in the coupling reaction was ob- several reactions [20]. The NPs became a useful tool for catalyt- served, reaching high turnover numbers (TON up 104–105) in ic transformations due to their excellent performance, which is the presence of aryl iodides and bromides. Additionally, the related to their small size and a high surface-to-volume ratio performance of the NPs was briefly examined for the [21-25]. Moreover, they are relatively easy to prepare and can Mizoroki–Heck reaction with haloacetophenones [47]. As a be obtained in different size and morphology by essentially remarkable feature of this nanocatalyst, besides its great cata- controlling the synthetic method and experimental conditions. lyst activity and compatibility with aqueous reaction media, is As a result of the excellent catalytic activity of NPs, they can be that it can be used without previous purification processes. used under mild and, in some cases, in environmental sustain- Consequently, as a part of our ongoing interest in developing able conditions. In particular, Pd NPs have been well-estab- green reaction conditions for organic syntheses; we herein lished as catalysts in the Mizoroki–Heck coupling reaction, ob- report an extensive study on the catalytic application of the taining the desired products in good to high yields, finding electrochemical synthesized PVP-Pd NPs for Mizoroki–Heck some examples in aqueous solution and under microwave coupling reaction. By the efficient coupling reaction with aryl (MW) irradiation [26-36]. Besides these studies, there is consid- bromides, many stilbenes and novel hetero-stilbenes were ob- erable room for improvements of the reported catalytic systems, tained employing the Pd NPs in aqueous medium under rela- which may involve high catalyst loadings (>1 mol %), toxic sol- tively mild conditions, using MW irradiation. vents, or limited application scope of iodoarenes and olefins [19]. Results and Discussion The PVP-Pd NPs of a mean diameter of 10 nm were obtained Along with the increasing awareness about the development of using a platinum electrode, characterized as previously re- sustainable catalysts, additional efforts should be made to ported, and used without additional purification [46,47]. In a address also sustainable reaction conditions; like employing previous work the PVP-Pd NPs synthesized using a vitreous ecological solvents and alternative energy input among others carbon electrode were tested on the Mizoroki–Heck reaction aspects [37,38]. Water represents a very attractive medium as a with 4-iodo- or 4-bromoacetophenone and styrene [47]. The result of its advantages as solvent (nontoxic, not flammable, best result with 4-bromoacetophenone was accomplished when cheap and readily available), the use of water or aqueous the reaction was performed under MW irradiation for systems as solvent in organic synthesis to replace hazardous and 10 minutes using 0.2 mol % of Pd, affording the (E)-stilbene expensive organic solvents have been explored [39,40]. Various product in 98% yield. In order to further explore the scope of catalytic systems have been reported for the Mizoroki–Heck the PVP-Pd NPs-catalyzed Mizoroki–Heck coupling, a system- reaction in aqueous medium [41-43]. However, a drawback of atic study of the reaction was carried out with a wide range of using water is related to the limited solubility of the reactants, substrates and olefins. Based on our previous results [47], and leading to less efficient reactions. To solve this problem several other reported examples of Mizoroki–Heck coupling reactions systems have been developed by using co-solvents, surfactants, that use MW irradiation as alternative energy input pressure reactors or heating the reaction mixture by MW irradi- [26,28,36,49], the reaction of 4-bromoacetophenone (1a) and ation [44]. Under MW irradiation conditions, not only the rate styrene (2a) as coupling reagents was initially selected to of organic reactions could be increased, and better selectivities screening the reaction conditions (Table 1). In this case, the of the products achieved, but also the homogeneous mixing of reactions were performed with 0.1 mol % of Pd, in a mixture of the reactants in water could be enhanced, on the basic of the H2O/alcohol (3:1) as solvent under MW irradiation, employing efficient ability to absorb MW energy by water [44]. The use of a dynamic heating method at fixed temperature in a sealed water in combination with MW heating for Heck coupling reac- vessel. The results are summarized in Table 1. tions has been reported, using a phase-transfer agent and focusing on the employment of ultralow catalyst concentrations A general screening was performed to determine the optimal [45]. reaction time, the identity and presence of a co-solvent (ethanol, isopropanol, ethylene glycol) and the best base (K2CO3, Recently, we reported the electrochemical synthesis of stable Pd Na2CO3, K3PO4, sodium acetate (NaOAc)). In a first approach, NPs by using platinum or vitreous carbon electrodes at room time optimization was performed by using K2CO3 as base, at 1718 Beilstein J. Org. Chem. 2017, 13, 1717–1727. Table 1: Reaction condition optimizations.a Entry Solvent Base t (min) Yield (%)b 1 H2O/EtOH K2CO3 1 65 2 H2O/EtOH K2CO3 5 92 3 H2O/EtOH K2CO3 10 100 c 4 H2O/EtOH K2CO3 10 88 5 H2O K2CO3 10 23 6 H2O/iPrOH K2CO3 10 100 7 H2O/ethylene glycol K2CO3 10 54 d 8 H2O/EtOH K2CO3 10 100 9 H2O/EtOH Na2CO3 10 100 10 H2O/EtOH K3PO4 10 93 11 H2O/EtOH NaOAc 10 54 12 H2O/EtOH – 10 <5 e 13 H2O/EtOH K2CO3 10 73 aReaction conditions: 0.25 mmol of 4-bromoacetophenone (1a), 0.30 mmol of styrene (2a), 0.5 mmol of the base, 0.1 mol % of Pd, 2 mL of the mixed solvent 3:1, 130 °C MW (dynamic heating method) in a sealed vessel. bGC yields. The yields reported represent at least the average of two reactions. c d e Pd loading of 0.05 mol %. Tap water. Catalyst source: H2PdCl4 0.5 mM + 16 g/L PVP. 130 °C by MW irradiation (entries 1–3, Table 1). The highest system was evaluated. For that, the Mizoroki–Heck coupling catalytic activity of PVP-Pd NPs was obtained after 10 minutes, reaction was carried out with a homogeneous mixture based on when the yield of stilbene 3 achieved 100% (entry 3, Table 1). H2PdCl4 and PVP (the same solution employed to obtain PVP- Reducing the catalyst loading (0.05 mol %) leads to a decrease Pd NPs by electroreduction, entry 13, Table 1). Under the same of product yield, however, to a very respectable 88% yield reaction conditions, this in situ arranged catalytic system proved (entry 4, Table 1). To achieve a complete conversion with this to be less active than the electrochemically preformed Pd NPs.
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